Hypophosphatasie – eine seltene Knochenstoffwechselerkrankung

Zusammenfassung

Die Hypophosphatasie (HP) ist eine seltene, meist autosomal rezessiv vererbte Erkrankung des Knochenstoffwechsels mit verminderter Aktivität der gewebeunspezifischen Alkalischen Phosphatase und konsekutiver Akkumulation von nicht abgebauten Stoffwechselprodukten. Sie ist charakterisiert durch eine generelle Störung der Knochenmineralisation mit nachfolgenden Knochendeformitäten, Frakturen und chronischer nicht-bakterieller Osteomyelitis. Weitere Symptome wie Nierenbeteiligung und Zahnveränderungen bzw. vorzeitiger Zahnverlust können auftreten. Kürzlich konnten wir zeigen, dass der klinische Phänotyp der infantiljuvenilen Form unter anderem durch Entzündung von Gelenken und Knochen beeinflusst wird. Akkumulierende Kalziumpyrophosphatkristalle scheinen hierbei von entscheidender Bedeutung zu sein. Zur Diagnosesicherung dienen laborchemische Analysen, humangenetische Tests sowie bildgebende Verfahren. Eine enge Anbindung an ein mit HP-Patienten erfahrenes Zentrum mit multidisziplinärer Betreuung ist von entscheidender Bedeutung. Da derzeit noch keine kurativen Therapien ausreichend evaluiert sind, stehen aktuell symptomatische Therapieansätze im Vordergrund der Behandlung.

Summary

Hypophosphatasia (HP) is an inborn error of bone metabolism transmitted predominantly as an autosomal-recessive trait. It is characterized by a reduced activity of the tissuenonspecific isoenzyme of alkaline phosphatase (TNSALP) and elevated concentrations of its substrates, including inorganic pyrophosphates. Calcium pyrophosphate crystals seem to be essentially involved in activating inflammatory signal transduction pathways via different receptors of the innate immune system. Clinical symptoms include defective bone mineralisation with bone deformities, fractures, chronic non-bacterial osteomyelitis, renal damage due to calcification, craniosynostosis and dental abnormalities with premature loss of dentition are further symptoms. Laboratory assays, genetic counselling and testing, and radiologic imaging can confirm the diagnosis. Because symptoms are highly variable in their clinical expression, patients should be followed by a HP-experienced multidisciplinary team. At the moment symptomatic support and treatment is most important because a more causative therapy, e. g. enzyme replacement therapy, is not yet available in Europe.

Schlüsselwörter

Hypophosphatasie - Knochenstoffwechsel - Alkalische Phosphatase - Kalziumpyrophosphatkristalle

Keywords

Hypophosphatasia - bone metabolism - alkaline phosphatase - calcium pyrophosphate crystals

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